Drops for Presbyopia: An Update

This is an exciting time for eye care. We are embarking on a new area of intervention where we now have one, and, likely will have many, pharmacologic treatments for presbyopia. These treatments generally fall into one of three mechanisms of action:

1. pupil constriction, 2. contraction of the ciliary body, or 3. lens-softening. For the early presbyope, and for those who don’t want to commit to a surgical intervention to improve spectacle-free near vision, having this treatment option is revolutionary.

Here, I discuss each of these pharmacologic treatments and where they stand.


Presenting Near-Vision Impairment

1 in 8
Americans ≥50 years have presenting near-vision impairment.

Functional Near-Vision Impairment

1 in 4
Americans ≥50 years have functional near-vision impairment.

Source: Zebardast N, Friedman DS, Vitale S. The Prevalence and Demographic Associations of Presenting Near-Vision Impairment Among Adults Living in the United States. Am J Ophthalmol. 2017;174:134-144. doi: 10.1016/j.ajo.2016.11.004. Epub 2016 Nov 16

Vuity (AbbVie)

  • Formula: Vuity is comprised of 1.25% pilocarpine hydrochloride with a proprietary vehicle. It was FDA approved in October 2021.
  • Mechanism of action: Pupil constriction and contraction of the ciliary body.
  • Clinical trial findings: The GEMINI 1 and GEMINI 2 phase 3 clinical studies showed a statistically significant number of subjects achieved 3 lines or more on a reading chart in low light, high-contrast distance-corrected near visual acuity (DCNVA), sans losing more than one line of corrected distance visual acuity at day 30 and hour 3. The most common adverse events were transient headache and red eye, occurring in >5% in participants.1
    My experience, thus far, in prescribing Vuity has been positive, with many patients delighted with regaining their functional near vision.

Brimochol PF (Visus Therapeutics)

  • Formula: Brimochol is comprised of carbachol 2.75%, brimonidine tartrate 0.1% and a proprietary vehicle.
  • Mechanism of action: Induction of a durable pupillary constriction and the creation of a pinhole effect that improves near visual acuity and depth of focus.
  • Clinical trial findings: The VIVID phase 2 clinical study revealed a minimum of 83% of subjects treated with Brimochol, Brimochol PF (preservative-free) or Carbachol PF gained 3 lines of improvement in binocular near visual acuity under mesopic conditions, sans losing 1 line of distance vision at 1 hour.2 Additionally, a minimum of 82%, 52%, and 35% of subjects achieved this endpoint at 3, 7, and 9 hours, respectively. Further, Brimochol and Brimochol PF provided a mean improvement in binocular near visual acuity of a minimum of 18 ETDRS letters, close to 4 lines, as early as 30 minutes, and a minimum of 12 letters at 9 hours. Brimochol, Brimochol PF, and Carbachol PF were well-tolerated, with the most common adverse events occurring >5% being temporary burning and stinging upon instillation.
  • Where it stands: In March, the phase 3 trials, BRIO-I and BRIO-II, were started.3

CSF-1 (Orasis Pharmaceuticals)

  • Formula: CSF-1 is a preservative-free drop comprised of pilocarpine 0.4% delivered in a proprietary vehicle.
  • Mechanism of action: Pupil constriction.
  • Clinical trial findings: Phase 3 clinical trials show CSF-1 provided a statistically significant 3 line or greater gain on a reading chart in DCNVA on day 8, without loss of 1 line or more in distance visual acuity.
    Additionally, 40% and 50% of subjects, respectively, achieved these 3 lines at all measured time points on day 1 and day 15, with subjects on day 15 showing a 3-line greater improvement in DCNVA as early as 20 minutes and up to 8 hours. The most common adverse events were headache and instillation site pain, occurring in 6.8% and 5.8% of participants, respectively.4
  • Where it stands. “To provide strategic options for CSF-1, Orasis plans to initiate a safety study with the option to extend long-term,”4 the company said.

(Lenz Therapeutics)

  • Formula: LNZ100/LNZ101 is a preservative-free drop that contains aceclidine 1.75%, with and without brimonidine for eye whitening.
  • Mechanism of action: pupil constriction.
  • Clinical trial findings: A phase 2b clinical trial showed 47.2% of subject eyes achieved at least 3 lines of near vision improvement on a reading chart 1 hour post-instillation, and 81% achieved at minimum 2 lines of near vision improvement.
    Also, 50% of subjects maintained a 2-line or more improvement up to 7 hours.
    Lenz Therapeutics said the drop was “well-tolerated, with no significant loss in monocular best-corrected distance visual acuity in study eyes, and no serious adverse events.”5|
  • Where it stands: phase 2C, phase 3 planned for second half of 2022.

MicroLine (Eyenovia)

  • Formula: MicroLine, by Eyenovia, is designed to mist a dose of 2% pilocarpine onto the ocular surface using its proprietary Micro-Array Print (MAP) Technology via the Optejet dispenser.
  • Mechanism of action: Pupil constriction.
  • Clinical trial findings: The Phase 3 clinical trial, VISION-1 showed a 3-line or more improvement in DCNVA versus placebo in low light conditions at 2 hours post-treatment.
    Adverse events were “all mild and transient in nature, including fewer than 3% of patients reporting brow/headache, according to the company.6
  • Where it stands: The VISION-2 clinical trial identified the primary endpoint as “improvement in high-contrast binocular DCNVA measured in low light conditions 2 hours post treatment.”


Glaukos Corporation announced this past January that it has begun a phase 2 clinical trial on its GLK-302 for the treatment of presbyopia. GLK-302 employs the company’s iLution platform’s patented cream-based drug formulation, which is applied to the outer surface of the eyelid.13 Pilocarpine is the active pharmacologic agent.

Nyxol + LDP
(Ocuphire Pharma, Inc.)

  • Formula: This drop utilizes preservative-free 0.75% phentolamine and 0.4% low-dose pilocarpine (LDP).
  • Mechanism of action: Pupil constriction.
  • Clinical trial findings: In the phase 2 clinical trial, VEGA-1, 61% of subjects improved ≥ 15 letters (3 lines) in photopic binocular near vision at 1 hour.
    Also, Nyxol + LDP showed durable near vision improvement through at least 6 hours. Adverse events were mild, transient conjunctival hyperemia, occurring in <5% of subjects.7
  • Where it stands: Ocuphire said it plans to move into phase 3 clinical trials.7

UNR844 (Novartis)

  • Formula: UNR844 is an ophthalmic solution of lipoic acid choline ester 1.5%.
  • Mechanism of action: Lens-softening.
  • Clinical trial findings: In a prospective, randomized, double-masked, and multicenter clinical trial, bilateral DCNVA improved in 53.1% of subjects, who reported gaining ≥10 letters.
    Also, these improvements were maintained at 5 and 7 months post-instillation.8
    UNR844 was well-tolerated, producing no clinically relevant changes in best-corrected distance visual acuity, pupil size, IOP, or discontinued use due to adverse events, reported the company.
  • Where it stands: The drop is currently undergoing a phase 2 trial.

VP1-001 (Viewpoint Therapeutics)

  • Formula: VP1-001 contains alpha-crystallin.9-12
  • Mechanism of action: Lens-softening.
  • Clinical trial findings: None at press time.
  • Where it stands: The drop is undergoing preclinical study for presbyopia and cataracts.9-12 CP

1. Abbvie. Press Releases. VUITY (pilocarpine HCI ophthalmic solution) 1.25%, the First and Only FDA-Approved Eye Drop to Treat Age-Related Blurry Near Vision (Presbyopia), is Now Available. Accessed May 6, 2022.
2. VISUS Therapeutics. Visus Therapeutics Announces Positive Topline Clinical Data from Phase 2 VIVID Study of BRIMOCHOL for the Treatment of Presbyopia. Accessed May 6, 2022.
3. Visus Therapeutics. Visus Therapeutics Initiates Phase 3 Pivotal Trials of BRIMOCHOL PF for the Treatment of Presbyopia. Accessed May 6, 2022. 
5. Eyefocus Formulations.
7. Ocuphire Pharma. Press Releases. Ocuphire’s VEGA-1 Phase 2 Trial in Presbyopia Meets Primary and Secondary Endpoints. ( . Accessed May 5, 2022. 2021.)
8. CISION. PR Newswire. Presbyopia Therapies Announces Primary Safety and Efficacy Endpoints met in a Phase IIb study of its Topical PRX Ophthalmic Solution for the Treatment of Presbyopia. Accessed May 5, 2022.
9. Korenfeld M, Robertson SM, Stein JM. Topical Topical lipoic acid choline ester eye drop for improvement of near visual acuity in subjects with presbyopia: a safety and preliminary efficacy trial. Eye (Lond). 2021;35(12):3292-3301.
10. (Makley LN, McMenimen KA, DeVree BT, et al. Pharmacological chaperone for α-crystallin partially restores transparency in cataract models. Science. 2015;350(6261):674-677.
11. Molnar KS, Dunyak BM, Su B, et al. Mechanism of action of VP1-001 in cryAB(R120G)-associated and age-related cataracts. Invest Ophthalmol Vis Sci. 2019;60:3320-3331.
12. Daszynski DM, Santhoshkumar P, Phadte AS, et al. Failure of oxysterols such as lanosterol to restore lens clarity from cataracts. Sci Rep. 2019;9:8459.
13. Glaukos. News Details. Glaukos Announces First Patient Enrolled in Phase 2 Clinical Trial for Presbyopia. Accessed May 5, 2022.